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Effects of single nucleotide polymorphisms on treatment outcomes and toxicity in patients treated with sunitinib

Chi Hoon Maeng1, Jun Ho Yi, Jeeyun Lee

  • 1Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Korea. hoy.lim@samsung.com.

Anticancer Research
|October 15, 2013
PubMed
Abstract

Insights

Single nucleotide polymorphisms (SNPs) in the Kinase insert domain receptor (KDR) gene may influence sunitinib treatment outcomes and toxicity in cancer patients. Specific KDR SNPs are linked to poorer survival and increased risk of severe anemia.

Area of Science:

  • Pharmacogenomics
  • Oncology
  • Molecular Biology

Background:

  • Sunitinib is a targeted therapy used for various cancers.
  • Genetic variations, specifically single nucleotide polymorphisms (SNPs), can influence drug efficacy and toxicity.
  • Vascular Endothelial Growth Factor Receptor (VEGFR) and Kinase insert domain receptor (KDR) are key targets in cancer therapy.

Purpose of the Study:

  • To investigate the association between SNPs in VEGFR and KDR genes and the efficacy and toxicity of sunitinib treatment.
  • To identify specific genetic markers that predict treatment response and adverse events in patients with gastric or biliary tract cancer.

Main Methods:

  • Retrospective analysis of 63 patients with gastric or biliary tract cancer treated with sunitinib.
  • Genotyping of eight VEGFA SNPs and five KDR SNPs.
  • Assessment of clinical outcomes, including time to treatment failure (TTF) and overall survival (OS), in relation to identified SNPs.
  • Evaluation of toxicity profiles, focusing on grade 3-4 anemia.

Main Results:

  • Specific VEGFA SNPs (rs2010963, rs833068) and KDR SNPs (rs1870377) were associated with poor TTF.
  • KDR SNPs rs1870377 and rs7692791 were linked to poorer OS.
  • Multivariate analysis confirmed rs1870377 as a significant predictor for both TTF and OS.
  • KDR SNP rs1531289 was associated with an increased risk of grade 3-4 anemia.

Conclusions:

  • Certain single nucleotide polymorphisms in the KDR gene may impact sunitinib treatment outcomes, including efficacy and toxicity.
  • Genetic profiling of KDR SNPs could potentially aid in personalizing sunitinib therapy for cancer patients.
  • Further research is warranted to validate these findings and explore the clinical utility of KDR SNPs in predicting sunitinib response.
Keywords:
Single nucleotide polymorphismVEGFVEGFRbiliary tract cancergastric cancersunitinib

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